Iyad Jresat

Hepatoprotective effect of coenzyme Q10 in rats with acetaminophen toxicity.

The potential protective effect of coenzyme Q10 against acute liver injury induced by a single dose of acetaminophen (700 mg/kg, p.o.) was investigated in rats. Coenzyme Q10 treatment was given as two i.p. injections, 10 mg/kg each, at 1 and 12 h following acetaminophen administration. Coenzyme Q10 significantly reduced the levels of serum aminotransferases, suppressed lipid peroxidation, prevented the decreases of reduced glutathione and catalase activity, decreased the elevations of tumor necrosis factor-α and nitric oxide as well as attenuating the reductions of selenium and zinc ions in liver tissue resulting from acetaminophen administration. Histopathological liver tissue damage mediated by acetaminophen was ameliorated by coenzyme Q10. Immunohistochemical analysis revealed that coenzyme Q10 significantly decreased the acetaminophen-induced overexpression of inducible nitric oxide synthase, nuclear factor-κB, caspase-3 and p53 in liver tissue. It was concluded that coenzyme Q10 protects rat liver against acute acetaminophen hepatotoxicity, most probably through its antioxidant, anti-inflammatory and antiapoptotic effects.

Cardioprotective effect of cannabidiol in rats exposed to doxorubicin toxicity.

The potential protective effect of cannabidiol, the major non-psychotropic Cannabis constituent, was investigated against doxorubicin cardiotoxicity in rats. Cardiotoxicity was induced by six equal doses of doxorubicin (2.5mgkg(-1) i.p., each) given at 48h intervals over two weeks to achieve a total dose of 15mgkg(-1). Cannabidiol treatment (5mgkg(-1)/day, i.p.) was started on the same day of doxorubicin administration and continued for four weeks. Cannabidiol significantly reduced the elevations of serum creatine kinase-MB and troponin T, and cardiac malondialdehyde, tumor necrosis factor-α, nitric oxide and calcium ion levels, and attenuated the decreases in cardiac reduced glutathione, selenium and zinc ions. Histopathological examination showed that cannabidiol ameliorated doxorubicin-induced cardiac injury. Immunohistochemical analysis revealed that cannabidiol significantly reduced the expression of inducible nitric oxide synthase, nuclear factor-κB, Fas ligand and caspase-3, and increased the expression of survivin in cardiac tissue of doxorubicin-treated rats. These results indicate that cannabidiol represents a potential protective agent against doxorubicin cardiac injury.

Protective effect of telmisartan against cadmium-induced nephrotoxicity in mice.

AIMS To investigate the nephroprotective effect of telmisartan, the angiotensin II receptor antagonist, against renal injury induced by cadmium in mice. MAIN METHODS Mice received cadmium chloride at a dose of 1.2mg Cd/kg/day, s.c., for nine weeks. Telmisartan treatment (1mg/kg/day, orally) was started one week before cadmium administration and continued for ten weeks. KEY FINDINGS Telmisartan significantly reduced blood urea nitrogen (BUN) and serum creatinine levels which were increased by cadmium. Also, telmisartan significantly suppressed lipid peroxidation, compensated deficits in the antioxidant defenses [reduced glutathione (GSH) level and catalase activity], decreased the elevations of tumor necrosis factor-α (TNF-α), nitric oxide (NO) and cadmium ion concentration, and attenuated the reductions of selenium and zinc ions in renal tissue resulted from cadmium administration. Histopathological examination revealed that cadmium-induced renal tissue damage was ameliorated by telmisartan treatment. Immunohistochemical analysis revealed that telmisartan significantly decreased the cadmium-induced overexpression of inducible nitric oxide synthase (iNOS), nuclear factor-κB (NF-κB), Fas ligand (FasL) and caspase-3 in renal tissue. SIGNIFICANCE Telmisartan, through its antioxidant and anti-inflammatory actions, effectively prevented cadmium nephrotoxicity in mice. Hence, telmisartan represents a potential candidate to protect the kidney from the detrimental effect of cadmium toxicity.

Telmisartan treatment attenuates arsenic-induced hepatotoxicity in mice

The protective effect of telmisartan, the angiotensin II-receptor antagonist, against liver toxicity induced by sodium arsenite (5 mg/kg/day, p.o., for 30 days) was investigated in mice. Telmisartan treatment (10 mg/kg/day, p.o.) was applied for 30 days, starting on the same day of arsenic administration. Telmisartan significantly reduced serum alanine aminotransferase level which was increased by sodium arsenite. Telmisartan significantly suppressed lipid peroxidation, and prevented the reduced glutathione depletion and nitric oxide elevation in the liver tissue resulted from arsenic administration. Also, the increase of arsenic ion, and the reductions of selenium and zinc ions in liver tissue were attenuated by telmisartan. Histopathological examination showed that liver tissue injury mediated by arsenic was ameliorated by telmisartan treatment. Immunohistochemical analysis revealed that telmisartan significantly decreased the arsenic-induced expression of inducible nitric oxide synthase, tumor necrosis factor-α, cyclooxygenase-2, nuclear factor-κB and caspase-3 in liver tissue. It was concluded that telmisartan may represent a potential option to protect the liver tissue from the detrimental effects of arsenic toxicity.

Therapeutic potential of cannabidiol against ischemia/reperfusion liver injury in rats

The therapeutic potential of cannabidiol, the major non-psychotropic Cannabis constituent, was investigated in rats exposed to ischemia/reperfusion liver injury. Ischemia was induced by clamping the pedicle of the left hepatic lobe for 30 min, and cannabidiol (5mg/kg, i.v.) was given 1h following the procedure and every 24h thereafter for 2 days. Ischemia/reperfusion caused significant elevations of serum alanine aminotransferase and hepatic malondialdehyde, tumor necrosis factor-α and nitric oxide levels, associated with significant decrease in hepatic reduced glutathione. Cannabidiol significantly attenuated the deterioration in the measured biochemical parameters mediated by ischemia/reperfusion. Histopathological examination showed that cannabidiol ameliorated ischemia/reperfusion-induced liver damage. Immunohistochemical analysis revealed that cannabidiol significantly reduced the expression of inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-κB, Fas ligand and caspase-3, and increased the expression of survivin protein in ischemic/reperfused liver tissue. These results emphasize that cannabidiol represents a potential therapeutic option to protect the liver against hypoxia-reoxygenation injury.

Protective effects of captopril in diabetic rats exposed to ischemia/reperfusion renal injury

To investigate the potential protective effects of captopril, the angiotensin‐converting enzyme inhibitor, in diabetic rats exposed to ischaemia/reperfusion (I/R) renal injury.

Therapeutic effect of coenzyme Q10 against experimentally-induced hepatocellular carcinoma in rats

The therapeutic potential of coenzyme Q10 was investigated in rats with hepatocellular carcinoma induced by trichloroacetic acid (0.5g/kg/day, p.o., for five days). Coenzyme Q10 treatment (0.4mg/kg/day, i.p.) was applied for four weeks following trichloroacetic acid administration. Coenzyme Q10 significantly suppressed lipid peroxidation, prevented the depletion of reduced glutathione and superoxide dismutase activity, and decreased the elevations of tumor necrosis factor-α and nitric oxide in liver tissue of rats with hepatocellular carcinoma. Also, the histopathological dysplastic changes induced by trichloroacetic acid in liver tissue were ameliorated by coenzyme Q10. Immunohistochemical analysis revealed that coenzyme Q10 significantly decreased the expression of hepPar-1, alpha-fetoprotein, inducible nitric oxide synthase, cyclooxygenase-2 and nuclear factor-κB in liver tissue of rats with hepatocellular carcinoma. It was concluded that coenzyme Q10 may represent a potential therapeutic option for liver carcinogenesis.

Captopril and telmisartan treatments attenuate cadmium-induced testicular toxicity in rats

The possible protective effect of captopril, an angiotensin‐converting enzyme inhibitor, vs. telmisartan, an angiotensin II‐receptor antagonist, was investigated in rats with testicular injury induced by a single i.p. injection of cadmium chloride (2 mg/kg). Captopril (60 mg/kg/day, p.o.) and telmisartan (10 mg/kg/day, p.o.) were given for five consecutive days, starting 3 days before cadmium administration. Both agents significantly increased serum testosterone level, which was reduced by cadmium, suppressed lipid peroxidation, restored the depleted reduced glutathione, decreased the elevations of nitric oxide, tumor necrosis factor‐α, and cadmium ion levels, and attenuated the reductions of selenium and zinc ions in testicular tissue resulted from cadmium administration. Immunohistochemical analysis revealed that both captopril and telmisartan significantly reduced the cadmium‐induced expression of inducible nitric oxide synthase, nuclear factor‐κB, Fas ligand, and caspase‐3 in testicular tissue. The differences between the results obtained with captopril and telmisartan were insignificant, suggesting that both drugs equally protected the testicular tissue from the detrimental effects of cadmium.

Cannabidiol treatment ameliorates ischemia/reperfusion renal injury in rats

AIMS To investigate the protective effect of cannabidiol, the major non-psychotropic Cannabis constituent, against renal ischemia/reperfusion injury in rats. MAIN METHODS Bilateral renal ischemia was induced for 30 min followed by reperfusion for 24h. Cannabidiol (5mg/kg, i.v.) was given 1h before and 12h following the procedure. KEY FINDINGS Ischemia/reperfusion caused significant elevations of serum creatinine and renal malondialdehyde and nitric oxide levels, associated with a significant decrease in renal reduced glutathione. Cannabidiol significantly attenuated the deterioration in the measured biochemical parameters induced by ischemia/reperfusion. Histopathological examination showed that cannabidiol ameliorated ischemia/reperfusion-induced kidney damage. Immunohistochemical analysis revealed that cannabidiol significantly reduced the expression of inducible nitric oxide synthase, tumor necrosis factor-α, cyclooxygenase-2, nuclear factor-κB, Fas ligand and caspase-3, and increased the expression of survivin in ischemic/reperfused kidney tissue. SIGNIFICANCE Cannabidiol, via its antioxidant and anti-inflammatory properties, may represent a potential therapeutic option to protect against ischemia/reperfusion renal injury.

Therapeutic role of telmisartan against acetaminophen hepatotoxicity in mice.

The therapeutic potential of telmisartan was investigated in mice exposed to acute hepatotoxicity induced by a single dose of acetaminophen (500 mg/kg, p.o.). Telmisartan treatment (two i.p. injections, 10mg/kg, each) was given at 1 and 12h following acetaminophen administration. Telmisartan significantly reduced the level of serum alanine aminotransferase, and suppressed lipid peroxidation, prevented the depletion of the antioxidant defenses (reduced glutathione level, and catalase and superoxide dismutase activities), and attenuated the elevation of nitric oxide resulted from acetaminophen administration. Also, telmisartan ameliorated the histopathological liver tissue damage induced by acetaminophen. Immunohistochemical analysis revealed that telmisartan significantly decreased the expression of inducible nitric oxide synthase, tumor necrosis factor-α, cyclooxygenase-2, nuclear factor-κB and caspase-3 in liver tissue of mice received acetaminophen overdose. In conclusion, telmisartan can be considered as a potential therapeutic option to protect against acute acetaminophen hepatotoxicity commonly encountered in clinical practice.